Seroprevalence of Neutralizing Antibodies Against Japanese Encephalitis Virus Among 6 Years Old Children With 5 Different Immunization Strategies in Zhejiang Province

Seroprevalence of Neutralizing Antibodies Against Japanese Encephalitis Virus Among 6 Years Old Children With 5 Different Immunization Strategies in Zhejiang Province, China: An Open-labeled, Ambidirectional Cohort Study

This study is to evaluate the seroprevalence of neutralizing antibodies against Japanese encephalitis (JE) virus in children aged 6 years who were previously administered with 5 different immunization strategies by JE attenuated live vaccine (JEV-L) or/and inactivated vaccine (JEV-I). The secondary objective is to evaluate the immunogenicity of the booster dose of JEV-I at 6 years old for those previously immunized with 3 doses of JEV-I or those sequential administered with 1 dose of JEV-L and another dose of JEV-I.

Study Overview

Detailed Description

Based on the retrospective registry in Zhejiang Provincial Immunization Information System, healthy children aged 6 years from 5 cohorts were included according to their previous immunization schedules on JE: 3 doses of JEV-I (Group 1), JEV-L+ JEV-I (Group 2), JEV-L+ JEV-I + JEV-I (Group 3), JEV-I + JEV-I+ JEV-L (Group 4), and 2 doses of JEV-L (Group 5). According to immunization programs in China, a booster dose of JEV-I is needed at the age of 6 for Group 1 and Group 2. A pre-vaccination blood sample (2.5ml) will be collected to evaluate the proportions of seropositivity before the booster dose of JEV-I. A second blood sample will be collected 28-35 days after the booster dose. Immunogenicity of the booster dose will be assessed by seroconversion rates, proportions of seropositivity and GMTs for these two groups. In addition, safety will be assessed with the occurrence of adverse events reported in these two groups. For the rest three groups who have completed the immunization schedules on JE, only one blood sample will be taken at the age of 6 to evaluate the proportions of seropositivity and GMTs after 4 years post the complete immunization schedules. Plague reduction neutralization test (PRNT) against both vaccine strains (SA-14-14-2 strain for JEV-L and Beijing P3 strain for JEV-I) will be used to test neutralizing antibody titers, so as to avoid potential bias in favor of either vaccine. PRNT50 titers (the reciprocal of the serum dilution that reduced the virus plaque count by 50% compared with the virus-only controls) ≥ 1:10 are deemed as positive.

Study Type

Interventional

Enrollment (Actual)

712

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Zhejiang
      • Lishui, Zhejiang, China, 323000
        • Liandu Center for Disease Control and Prevention
      • Quzhou, Zhejiang, China, 324000
        • Kecheng center for disease control and prevention
      • Wenzhou, Zhejiang, China, 325400
        • Pingyang center for disease control and prevention

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 6 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participants aged ≥ 72 months to < 75 months.
  • Participants have completed routine immunization schedules in time.
  • Participants are healthy native residents.
  • Parents/guardians can understand the protocol requirements, provide informed consent, accept all scheduled visits, and comply with all trial procedures.

Exclusion Criteria:

  • History of neurological diseases or related symptoms.
  • An acute illness with fever (temperature ≥ 37.1℃) or any acute onset of chronic diseases.
  • Known impairment of immunologic function, or receipt of immunosuppressive therapy or immunoglobulin in the past 3 months.
  • Known allergy to any constituent of the vaccine.
  • Have been injected with other vaccines or any clinical trial drugs in the past 4 weeks.
  • Any condition which, in the opinion of the investigator, would pose a health risk to the subject or interfere with the vaccine.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 3JEV-I (Group 1)

Retrospective: 3 doses of JE vaccines. 2 doses of Inactivated JE Vaccine (JEV-I, 7-10 days apart) at 8 months of age and 1 dose of JEV-I at 2 years old.

Prospective: 1 booster dose of JEV-I at 6 years old.

The investigators recruit 6 years old children who have been vaccinated by 2-3 doses of JE vaccines with different immunization strategies. For participants from Group 1 and Group 2 who haven't completed the JE immunization schedules, a booster dose of JEV-I will be administered at 6 years old.
Experimental: JEV-L+JEV-I (Group 2)

Retrospective: 2 doses of JE vaccines.

1 dose of JE attenuated live vaccine (JEV-L) at 8 months of age and 1 dose of JEV-I at 2 years old.

Prospective: 1 booster dose of JEV-I at 6 years old.

The investigators recruit 6 years old children who have been vaccinated by 2-3 doses of JE vaccines with different immunization strategies. For participants from Group 1 and Group 2 who haven't completed the JE immunization schedules, a booster dose of JEV-I will be administered at 6 years old.
Experimental: JEV-L+2JEV-I (Group 3)

Retrospective: 3 doses of JE vaccines.

1 dose of JEV-L at 8 months of age and 2 dose (7-10 days apart) of JEV-I at 2 years old.

The investigators recruit 6 years old children who have been vaccinated by 2-3 doses of JE vaccines with different immunization strategies. Participants from Group 3-5 have completed the JE immunization schedules with JEV-I or/and JEV-L. No prospective intervention will be given.
Experimental: 2JEV-I+JEV-L (Group 4)
Retrospective: 3 doses of JE vaccines. 2 doses of JEV-I (7-10 days apart) at 8 months of age and 1 dose of JEV-L at 2 years old.
The investigators recruit 6 years old children who have been vaccinated by 2-3 doses of JE vaccines with different immunization strategies. Participants from Group 3-5 have completed the JE immunization schedules with JEV-I or/and JEV-L. No prospective intervention will be given.
Experimental: 2JEV-L (Group 5)
Retrospective: 2 doses of JE vaccines. 2 doses of JEV-L respectively administered at 8 months of age and 2 years old.
The investigators recruit 6 years old children who have been vaccinated by 2-3 doses of JE vaccines with different immunization strategies. Participants from Group 3-5 have completed the JE immunization schedules with JEV-I or/and JEV-L. No prospective intervention will be given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportions of seropositivity of neutralizing antibodies against JE at the age of 6
Time Frame: At the age of 6. Test immediately after enrollment by a dose of blood sample.
Defined as any positive antibody (neutralizing antibody titers ≥1:10) response in children aged 6.
At the age of 6. Test immediately after enrollment by a dose of blood sample.
Geometric Mean Titers (GMTs) or Median antibody titers for children aged 6 years
Time Frame: At the age of 6. Test immediately after enrollment by a dose of blood sample.
Neutralizing antibody titers by plaque-reduction neutralization tests (PRNT).
At the age of 6. Test immediately after enrollment by a dose of blood sample.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Seroconversion rates of the booster dose of JEV-I for Group 1 and Group 2
Time Frame: before and 28-35 days after the booster dose.
Defined as any positive antibody (neutralizing antibody titers ≥1:10) response in children who were seronegative prior to the booster dose, or at least a four-fold increase for children who had pre-existing positive antibodies.
before and 28-35 days after the booster dose.
Proportion of seropositivity of neutralizing antibodies against JE after the booster dose for Group 1 and Group 2.
Time Frame: 28-35 days after the booster dose.
Defined as any positive antibody (neutralizing antibody titers ≥1:10) response after the booster dose.
28-35 days after the booster dose.
Geometric Mean Titers (GMTs) or Median antibody titers after the booster dose for Group 1 and Group 2.
Time Frame: 28-35 days after the booster dose.
Neutralizing antibody titers by PRNT.
28-35 days after the booster dose.
Safety of the booster dose for Group 1 and Group 2
Time Frame: From inoculation to 30 days after the inoculation.
The occurrence of adverse events for the booster dose
From inoculation to 30 days after the inoculation.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2021

Primary Completion (Actual)

September 17, 2022

Study Completion (Anticipated)

June 30, 2023

Study Registration Dates

First Submitted

March 23, 2021

First Submitted That Met QC Criteria

March 25, 2021

First Posted (Actual)

March 26, 2021

Study Record Updates

Last Update Posted (Actual)

November 15, 2022

Last Update Submitted That Met QC Criteria

November 13, 2022

Last Verified

July 1, 2022

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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